GCY8_CAEEL
ID GCY8_CAEEL Reviewed; 1152 AA.
AC Q9GYQ4; Q2L6K7;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Receptor-type guanylate cyclase gcy-8 {ECO:0000305};
DE EC=4.6.1.2 {ECO:0000269|PubMed:27062922};
DE Flags: Precursor;
GN Name=gcy-8 {ECO:0000312|WormBase:C49H3.1};
GN ORFNames=C49H3.1 {ECO:0000312|WormBase:C49H3.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:BAE78828.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16415369; DOI=10.1534/genetics.105.050013;
RA Inada H., Ito H., Satterlee J., Sengupta P., Matsumoto K., Mori I.;
RT "Identification of guanylyl cyclases that function in thermosensory neurons
RT of Caenorhabditis elegans.";
RL Genetics 172:2239-2252(2006).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND DOMAIN.
RX PubMed=21315599; DOI=10.1016/j.cub.2011.01.053;
RA Wasserman S.M., Beverly M., Bell H.W., Sengupta P.;
RT "Regulation of response properties and operating range of the AFD
RT thermosensory neurons by cGMP signaling.";
RL Curr. Biol. 21:353-362(2011).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY,
RP DOMAIN, AND MUTAGENESIS OF SER-110; CYS-141; GLY-707 AND GLU-1057.
RX PubMed=27062922; DOI=10.1016/j.cell.2016.03.026;
RA Singhvi A., Liu B., Friedman C.J., Fong J., Lu Y., Huang X.Y., Shaham S.;
RT "A glial K/Cl transporter controls neuronal receptive ending shape by
RT chloride inhibition of an rGC.";
RL Cell 165:936-948(2016).
CC -!- FUNCTION: Guanylate cyclase involved in the production of the second
CC messenger cGMP (PubMed:27062922). Regulates thermotaxis responses in
CC AFD sensory neurons (PubMed:16415369, PubMed:21315599,
CC PubMed:27062922). May regulate AFD neuronal activity such as calcium
CC responses to temperature gradients (PubMed:16415369, PubMed:21315599).
CC Maintains the microvilli receptive ending morphology of the AFD
CC thermosensory neurons by regulating cGMP levels downstream of kcc-3
CC (PubMed:27062922). cGMP levels antagonize the actin cytoskeleton
CC regulator wsp-1 (PubMed:27062922). {ECO:0000269|PubMed:16415369,
CC ECO:0000269|PubMed:21315599, ECO:0000269|PubMed:27062922}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000269|PubMed:27062922};
CC -!- ACTIVITY REGULATION: Inhibited by chloride with an IC(50) of 60 mM.
CC {ECO:0000269|PubMed:27062922}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Cell projection, cilium
CC {ECO:0000269|PubMed:16415369}. Note=Localizes exclusively to the
CC sensory ending, known as cilium, in AFD neurons.
CC {ECO:0000269|PubMed:16415369}.
CC -!- TISSUE SPECIFICITY: Expressed bilaterally in AFD sensory neurons.
CC {ECO:0000269|PubMed:16415369, ECO:0000269|PubMed:27062922}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. Might be required for the negative regulation of the
CC guanylate cyclase domain (PubMed:27062922). {ECO:0000255|PROSITE-
CC ProRule:PRU00159, ECO:0000269|PubMed:27062922}.
CC -!- DOMAIN: The guanylate cyclase domain is required for thermotaxis
CC responses. {ECO:0000269|PubMed:21315599, ECO:0000269|PubMed:27062922}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; AB201388; BAE78828.1; -; mRNA.
DR EMBL; FO080908; CCD67714.1; -; Genomic_DNA.
DR RefSeq; NP_501324.2; NM_068923.4.
DR AlphaFoldDB; Q9GYQ4; -.
DR SMR; Q9GYQ4; -.
DR STRING; 6239.C49H3.1; -.
DR EPD; Q9GYQ4; -.
DR PaxDb; Q9GYQ4; -.
DR PeptideAtlas; Q9GYQ4; -.
DR EnsemblMetazoa; C49H3.1.1; C49H3.1.1; WBGene00001535.
DR GeneID; 177584; -.
DR KEGG; cel:CELE_C49H3.1; -.
DR UCSC; C49H3.1; c. elegans.
DR CTD; 177584; -.
DR WormBase; C49H3.1; CE42080; WBGene00001535; gcy-8.
DR eggNOG; KOG1023; Eukaryota.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; Q9GYQ4; -.
DR OMA; TKVQCRL; -.
DR OrthoDB; 90908at2759; -.
DR PhylomeDB; Q9GYQ4; -.
DR BRENDA; 4.6.1.2; 1045.
DR PRO; PR:Q9GYQ4; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00001535; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031528; C:microvillus membrane; IDA:WormBase.
DR GO; GO:0044306; C:neuron projection terminus; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0016048; P:detection of temperature stimulus; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0032528; P:microvillus organization; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; ISS:WormBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0040040; P:thermosensory behavior; IMP:UniProtKB.
DR GO; GO:0043052; P:thermotaxis; IMP:UniProtKB.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cell projection; cGMP biosynthesis;
KW Coiled coil; Glycoprotein; GTP-binding; Lyase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1152
FT /note="Receptor-type guanylate cyclase gcy-8"
FT /evidence="ECO:0000255"
FT /id="PRO_0000433277"
FT TOPO_DOM 22..506
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 507..527
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 528..1152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 567..857
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 927..1057
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT COILED 861..899
FT /evidence="ECO:0000255"
FT BINDING 573..581
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 593
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 932
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 932
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 933
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 976
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 976
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 465
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 110
FT /note="S->E: Reduced basal guanylate cyclase activity and
FT reduced chloride sensitivity."
FT /evidence="ECO:0000269|PubMed:27062922"
FT MUTAGEN 141
FT /note="C->S: Reduced basal guanylate cyclase activity and
FT reduced chloride sensitivity."
FT /evidence="ECO:0000269|PubMed:27062922"
FT MUTAGEN 707
FT /note="G->E: In ns335; enhanced basal guanylate cyclase
FT activity. Exhibits fewer and shorter microvilli of the AFD
FT thermosensory neurons. Defects in thermotaxis."
FT /evidence="ECO:0000269|PubMed:27062922"
FT MUTAGEN 1057
FT /note="E->A: Enhanced basal guanylate cyclase activity."
FT /evidence="ECO:0000269|PubMed:27062922"
SQ SEQUENCE 1152 AA; 129070 MW; 5B477735913F2ADD CRC64;
MRTKKAFLLL TFNVLIYLAA CQETERILAN NGTEDNEITT SKGVSPNTNP LFLSNSTAGL
YDSKGRIRLT IGHIGAIGAL RNDVKILEVS HKALQAEGIL DDDLDVEIIS QTGCGESYEG
VAVAADMYHL QKVKAFIGPY CNAEMDAVAR MAAFWNIPII GYMAASNNLA DKNAYPTLAR
ISLRTTNSIA EATCAMLRHY GWNKVAIITN TGILAYDRVL SFEEVFHQRG INVVKKIMFD
EFADSKAMIA SGLLNDIKNS ARIVVCLFSN TRESSREFLT AANTQGMNVN EYGYVFPWLQ
DGGKDASPWT GADGSMLQKV KDQYANAIII DDVNSFDNTI VGPFIERIKD VGLTEADVDI
ANIYGYLYLF DALKLYAIAA RKVLNETGKA ENLLNGRMMW QNMRKLKFVG MVGASGIASG
QVSMDDRAER APLYRGFFVS PNSDSVLPMV HMEPTMLDNC DGIANKSGCY EIVVTDIMRD
FWPSVDRKMP KDEPDCGYRN ERCDYTLIII GAALILLFIV AAVSAFFAQK ILEKRALDKL
PFRIYRDDLQ FIDEEQLKSM LSLGSTRTKM SNMNYGSRNH AIVGTNTHAI YHKYVQRRPI
VFNRADKTLI QLMKAAVHDN INPFLGMVWN EREEMLLVWK FCSRGTLQDI IYNESIQLDT
KFHGAFIRDI LAGLEYLHAS QIGYHGSLTP WSCLIDRNWM IKLTDYGIAD PLERWEKSQS
ISRDGLTSDD DKSQATQATS ILYESPEMLK NREKNRVRRV DQDWMRQTQT RRQLGDVYAF
GLVMYEIIFR ALPFPEGTNQ SELVEWLRDG SKVVKPTIPQ NKVLNMDLSA LIQDCWNTTP
EMRPSLRRIK LNVETYLNIK GSLVDQMTRM MEQYANNLEK LVAERTGMLE EANQRADRLL
SQLLPAYVAN ELKLGRPVPP KTFTSSTVLF SDIVGFTEMC QNASPLEVVA VLNGIFDGFD
QFIARKDAYK VETIGDAYMV VSGVPEENGH RHINEIASIA LDVHKFLSEF IVPHKRDTKV
QCRLGFHTGP VAAAVVGLNA PRYCLFGDTV NMASRMESNS EPGKTQISET AKNLLLKEYP
DYICEQRGEI PIKGKGLCMT YWLMGTKSEG SGRSGAYLAP SMKSAGTGFT GMLGNSANDY
SLNLKNPTGL QR
